Dr Cosman on the Potential Utility of MT-302 in TROP-2–Expressing Epithelial Cancers

Rasha Cosman, BSc, MBBS, FRACP, staff specialist, head, Early Phase Clinical Trials Unit, Kinghorn Cancer Centre, St Vincent’s Hospital; conjoint senior lecturer, University of New South Wales (UNSW), discusses the unique mechanism of action of the novel in vivo mRNA CAR therapy MT-302, highlighting its potential role in the treatment of patients with TROP-2–expressing epithelial cancers.

MT-302 is an innovative therapeutic leveraging novel mRNAs wrapped in lipid nanoparticles delivered by standard intravenous infusions to specifically reprogram a patient’s myeloid cells, Cosman begins. This therapy is designed to target TROP-2, a protein commonly overexpressed in various epithelial tumors, she notes. By harnessing the power of these reprogrammed cells, MT-302 aims to initiate a comprehensive antitumor immune response by infiltrating the tumor microenvironment and attacking cancer cells, Cosman explains.

The phase 1 MYE Symphony trial (NCT05969041) is a first-in-class study which is evaluating the novel CAR-myeloid (CAR-M) therapy in patients with advanced epithelial cancers that exhibit high TROP-2 expression, Cosman states. This phase 1 trial is primarily focused on establishing safety, determining the maximum-tolerated dose, and identifying the recommended phase 2 dose of the agent. Key secondary end points include evaluating the pharmacokinetics of the therapy and monitoring for immune-related adverse effects. Exploratory end points include assessing the therapy’s efficacy, as measured by overall response rate and duration of response. Additionally, the trial will examine the immunologic effects of treatment, looking at factors like peripheral CAR expression, cytokine release, and T-cell receptor clonality, as well as changes in the tumor immune environment and TROP-2 expression.

Three dose level cohorts have already been enrolled, and early signals of activity are promising, Cosman reports. If MT-302 is proven to be safe and effective, it could become an important therapeutic option for patients with TROP-2–expressing epithelial cancers, potentially overcoming many of the challenges experienced with ex vivo CAR therapies, she concludes.